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Role of circFAM188A in EOC Autophagy Through miR-670-3P and ULK1

September, 09, 2024 | Gynecologic Cancer, Ovarian Cancer

KEY TAKEAWAYS

  • The study aimed to investigate how circFAM188A regulates autophagy and invasion in OC via miR-670-3p and ULK1.
  • Researchers noticed that circFAM188A modulates autophagy in OC by sponging miR-670-3p and interacting with ULK1.

CircRNAs and autophagy play significant roles in the physiological and pathological processes of ovarian cancer (OC), yet their precise mechanisms remain unclear.

Min Yong and the team aimed to focus on elucidating the role and pathways of circFAM188A in epithelial ovarian carcinoma (EOC), examining its impact on proliferation, autophagy, and invasion.

They performed an inclusive analysis by assessing the expression of circFAM188A in tissues from patients with EOC using RT-PCR. To investigate the roles of circFAM188A in proliferation, invasion, and autophagy in tumor cells, Transwell, 5-ethynyl-2′-deoxyuridine (EdU), and mRFP-GFP-LC3 reporter assays were employed.

Bioinformatics predicted the binding sites between circFAM188A and miR-670-3p, as well as between miR-670-3p and YY1, which were subsequently validated using dual-luciferase reporter assays. Pulldown assays confirmed the interaction between ULK1 and circFAM188A, with ULK1 being identified as critical in the early stages of autophagy. Additionally, an in vivo xenograft model was established by subcutaneously injecting nude mice with EOC cells.

Results showed that expression of circ-FAM188A was increased in EOC tissues relative to normal ovarian tissues, and circ-FAM188A overexpression promoted proliferation, invasion, and autophagy; these effects were reversed by circ-FAM188A silencing. miR-670-3p and circ-FAM188A co-localized in the cytoplasm. circ-FAM188A enhanced YY1 expression by sponging miR-670-3p and was also shown to interact with ULK1.

The study concluded that circ-FAM188A modulates autophagy by sponging miR-670-3p and interacting with ULK1.

This study was funded by the Sichuan Science and Technology Program (2022NSFSC1357); the Nanchong City-School Science and Technology Strategic Cooperation Project (19SXHZ0293); Doctoral Initiation Fund Project (Natural Science) (CBY21-QD23); the Key Scientific Research Project of North Sichuan Medical College (CBY18-A-ZD21), the Scientific Research Project of Affiliated Hospital of North Sichuan Medical College (2020JC021), the National Science Foundation of China (82103250), Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (kryc-yq-2104 and kryc-yq-2222), Traditional Chinese Medicine research joint project of Chongqing Health Commission and Chongqing Science and Technology Bureau (2019ZY3152), and Senior Medical Talents Program of Chongqing for Young and Middle-aged.

Source: https://pubmed.ncbi.nlm.nih.gov/39229655/

Yong M, Zeng Y, Yao Y, et al. (2024). “CircFAM188A Regulates Autophagy via miR-670-3p and ULK1 in Epithelial Ovarian Carcinoma.” Cancer Rep (Hoboken). 2024;7(9):e2128. doi:10.1002/cnr2.2128

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